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https://www.readbyqxmd.com/read/28817786/propofol-attenuates-bv2-microglia-inflammation-via-nmda-receptor-inhibition
#1
Qichao Wu, Yanjun Zhao, Xiangyuan Chen, Minmin Zhu, Changhong Miao
Activated microglia, involved in the occurrence and improvement of sepsis-associated encephalopathy, can induce the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, resulting in inflammation-mediated neuronal cell death. It was reported that propofol could inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and pro-inflammatory enzymes expression in BV2 and primary microglial cells. However, the underlying mechanism is not well known. In the present study, we investigated whether and how propofol inhibited LPS-induced the expression of pro-inflammatory cytokines and pro-inflammatory enzymes in BV2 cells...
August 17, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28808323/stress-hormone-rapidly-tunes-synaptic-nmda-receptor-through-membrane-dynamics-and-mineralocorticoid-signalling
#2
Lenka Mikasova, Hui Xiong, Amber Kerkhofs, Delphine Bouchet, Harm J Krugers, Laurent Groc
Stress hormones, such as corticosteroids, modulate the transmission of hippocampal glutamatergic synapses and NMDA receptor (NMDAR)-dependent synaptic plasticity, favouring salient behavioural responses to the environment. The corticosterone-induced synaptic adaptations partly rely on changes in NMDAR signalling, although the cellular pathway underlying this effect remains elusive. Here, we demonstrate, using single molecule imaging and electrophysiological approaches in hippocampal neurons, that corticosterone specifically controls GluN2B-NMDAR surface dynamics and synaptic content through mineralocorticoid signalling...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807933/mice-deficient-in-lysophosphatidic-acid-acyltransferase-%C3%AE-lpaat%C3%AE-acylglycerophosphate-acyltransferase-4-agpat4-have-impairments-in-spatial-learning-and-memory-associated-with-reductions-in-nmda-and-ampa-receptors
#3
Ryan M Bradley, Emily B Mardian, Darin Bloemberg, Juan J Aristizabal Henao, Andrew S Mitchell, Phillip M Marvyn, Katherine A Moes, Ken D Stark, Joe Quadrilatero, Robin E Duncan
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here we report that Lpaatδ (-/-) mice display impaired spatial learning and memory compared to wildtype littermates in the Morris Water Maze, and investigated potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28803849/characteristics-of-ethanol-induced-behavioral-sensitization-in-rats-molecular-mediators-and-cross-sensitization-between-ethanol-and-cocaine
#4
Shijie Xu, Ung Gu Kang
Repeated exposure to drugs of abuse can induce a progressive increase in locomotor activity, known as behavioral sensitization. However, little is known about behavioral sensitization to ethanol. We examined whether ethanol could induce behavioral sensitization and investigated several molecular changes accompanying sensitization. We also assessed whether "cross-sensitization" occurred between ethanol and cocaine, another abused drug. Ethanol-induced sensitization was examined in rats after ethanol treatment (0...
August 10, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28801194/medial-septum-modulates-hippocampal-gamma-activity-and-prepulse-inhibition-in-an-n-methyl-d-aspartate-receptor-antagonist-model-of-schizophrenia
#5
L Stan Leung, Jingyi Ma
We reviewed the participation of the septohippocampal system in an animal model of schizophrenia that was acutely induced by systemic injection of an N-methyl-d-aspartate (NMDA) receptor antagonist such as phencyclidine, MK-801 and ketamine. The NMDA receptor antagonist-induced model of schizophrenia is characterized by behavioral and electrophysiological disruptions, including a decrease in prepulse inhibition of the acoustic startle response (PPI), hyperlocomotion, decrease in gating of hippocampal auditory evoked potentials and robust increase in hippocampal gamma (30-100Hz) oscillations...
August 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28795439/g-protein-coupled-receptor-37-like-1-modulates-astrocyte-glutamate-transporters-and-neuronal-nmda-receptors-and-is-neuroprotective-in-ischemia
#6
Sarah Jolly, Narges Bazargani, Alejandra C Quiroga, Nigel P Pringle, David Attwell, William D Richardson, Huiliang Li
We show that the G protein-coupled receptor GPR37-like 1 (GPR37L1) is expressed in most astrocytes and some oligodendrocyte precursors in the mouse central nervous system. This contrasts with GPR37, which is mainly in mature oligodendrocytes. Comparison of wild type and Gpr37l1(-/-) mice showed that loss of GPR37L1 did not affect the input resistance or resting potential of astrocytes or neurons in the hippocampus. However, GPR37L1-mediated signalling inhibited astrocyte glutamate transporters and - surprisingly, given its lack of expression in neurons - reduced neuronal NMDA receptor (NMDAR) activity during prolonged activation of the receptors as occurs in ischemia...
August 10, 2017: Glia
https://www.readbyqxmd.com/read/28795276/topiramate-via-nmda-ampa-kainate-gabaa-and-alpha2-receptors-and-by-modulation-of-creb-bdnf-and-akt-gsk3-signaling-pathway-exerts-neuroprotective-effects-against-methylphenidate-induced-neurotoxicity-in-rats
#7
Majid Motaghinejad, Manijeh Motevalian, Sulail Fatima, Tabassom Beiranvand, Shiva Mozaffari
Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABAA receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D2 receptor antagonist...
August 9, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28790020/prenatal-choline-supplementation-attenuates-mk-801-induced-deficits-in-memory-motor-function-and-hippocampal-plasticity-in-adult-male-rats
#8
Chelsea A Nickerson, Alexandra L Brown, Waylin Yu, Yoona Chun, Melissa J Glenn
Choline is essential to the development and function of the central nervous system and supplemental choline during development is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders, particularly schizophrenia. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood...
August 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28782641/nitric-oxide-cgmp-signaling-via-guanylyl-cyclase-isoform-1-modulates-glutamate-and-gaba-release-in-somatosensory-cortex-of-mice
#9
Qi Wang, Evanthia Mergia, Doris Koesling, Thomas Mittmann
In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. NO-GC1 KO slices revealed reduced frequencies of miniature excitatory- and inhibitory-postsynaptic currents, increased paired-pulse ratios and decreased input-output curves of evoked signals, which indicated the reduction of glutamate and GABA release in NO-GC1 KO mice...
August 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28765142/a-retained-intron-in-the-3-utr-of-calm3-mrna-mediates-its-staufen2-and-activity-dependent-localization-to-neuronal-dendrites
#10
Tejaswini Sharangdhar, Yoichiro Sugimoto, Jacqueline Heraud-Farlow, Sandra M Fernández-Moya, Janina Ehses, Igor Ruiz de Los Mozos, Jernej Ule, Michael A Kiebler
Dendritic localization and hence local mRNA translation contributes to synaptic plasticity in neurons. Staufen2 (Stau2) is a well-known neuronal double-stranded RNA-binding protein (dsRBP) that has been implicated in dendritic mRNA localization. The specificity of Stau2 binding to its target mRNAs remains elusive. Using individual-nucleotide resolution CLIP (iCLIP), we identified significantly enriched Stau2 binding to the 3'-UTRs of 356 transcripts. In 28 (7.9%) of those, binding occurred to a retained intron in their 3'-UTR The strongest bound 3'-UTR intron was present in the longest isoform of Calmodulin 3 (Calm3L ) mRNA Calm3L 3'-UTR contains six Stau2 crosslink clusters, four of which are in this retained 3'-UTR intron...
August 1, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28758582/potential-novel-treatments-for-bipolar-depression-ketamine-fatty-acids-anti-inflammatory-agents-and-probiotics
#11
G H Vázquez, S Camino, L Tondo, Ross J Baldessarini
BACKGROUND: Treatments for depression in bipolar disorder (BD) are far less well developed than for unipolar major depressive disorder. Several innovative and experimental approaches have been emerging recently, including use of the dissociative anesthetic ketamine and other antagonists of central NMDA glutamate receptors, as well as unsaturated fatty acids, anti-inflammatory agents, and possibly probiotic methods. METHODS: We reviewed relevant reports from the past decade...
July 28, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28757327/differential-electrophysiological-and-morphological-alterations-of-thalamostriatal-and-corticostriatal-projections-in-the-r6-2-mouse-model-of-huntington-s-disease
#12
Anna Parievsky, Cindy Moore, Talia Kamdjou, Carlos Cepeda, Charles K Meshul, Michael S Levine
Huntington's disease (HD) is a fatal genetic disorder characterized by cell death of medium-sized spiny neurons (MSNs) in the striatum, traditionally attributed to excessive glutamate inputs and/or receptor sensitivity. While changes in corticostriatal projections have typically been studied in mouse models of HD, morphological and functional alterations in thalamostriatal projections have received less attention. In this study, an adeno-associated virus expressing channelrhodopsin-2 under the calcium/calmodulin-dependent protein kinase IIα promoter was injected into the sensorimotor cortex or the thalamic centromedian-parafascicular nuclear complex in the R6/2 mouse model of HD, to permit selective activation of corticostriatal or thalamostriatal projections, respectively...
July 27, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28756461/adolescent-stress-leads-to-glutamatergic-disturbance-through-dopaminergic-abnormalities-in-the-prefrontal-cortex-of-genetically-vulnerable-mice
#13
Yurie Matsumoto, Minae Niwa, Akihiro Mouri, Yukihiro Noda, Takeshi Fukushima, Norio Ozaki, Toshitaka Nabeshima
BACKGROUND: Stress during the adolescent period influences postnatal maturation and behavioral patterns in adulthood. Adolescent stress-induced molecular and functional changes in neurons are the key clinical features of psychiatric disorders including schizophrenia. OBJECTIVE: In the present study, we exposed genetically vulnerable mice to isolation stress to examine the molecular changes in the glutamatergic system involving N-methyl-d-aspartate (NMDA) receptors via dopaminergic disturbance in the prefrontal cortex (PFc)...
July 29, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28754372/endogenous-nitric-oxide-inhibits-spinal-nmda-receptor-activity-and-pain-hypersensitivity-induced-by-nerve-injury
#14
Shao-Rui Chen, Xiao-Gao Jin, Hui-Lin Pan
The role of nitric oxide (NO) in nociceptive transmission at the spinal cord level remains uncertain. Increased activity of spinal N-methyl-d-aspartate (NMDA) receptors contributes to development of chronic pain induced by peripheral nerve injury. In this study, we determined how endogenous NO affects NMDA receptor activity of spinal cord dorsal horn neurons in control and spinal nerve-ligated rats. Bath application of the NO precursor l-arginine or the NO donor S-nitroso-N-acetylpenicillamine (SNAP) significantly inhibited NMDA receptor currents of spinal dorsal horn neurons in both sham control and nerve-injured rats...
July 25, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28751664/afferent-specific-role-of-nmda-receptors-for-the-circuit-integration-of-hippocampal-neurogliaform-cells
#15
R Chittajallu, J C Wester, M T Craig, E Barksdale, X Q Yuan, G Akgül, C Fang, D Collins, S Hunt, K A Pelkey, C J McBain
Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component...
July 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28749937/recurrently-connected-and-localized-neuronal-communities-initiate-coordinated-spontaneous-activity-in-neuronal-networks
#16
Davide Lonardoni, Hayder Amin, Stefano Di Marco, Alessandro Maccione, Luca Berdondini, Thierry Nieus
Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs), interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28747405/nmda-receptor-dependent-presynaptic-inhibition-at-the-calyx-of-held-synapse-of-rat-pups
#17
Tomoko Oshima-Takago, Hideki Takago
N-Methyl-d-aspartate receptors (NMDARs) play diverse roles in synaptic transmission, synaptic plasticity, neuronal development and neurological diseases. In addition to their postsynaptic expression, NMDARs are also expressed in presynaptic terminals at some central synapses, and their activation modulates transmitter release. However, the regulatory mechanisms of NMDAR-dependent synaptic transmission remain largely unknown. In the present study, we demonstrated that activation of NMDARs in a nerve terminal at a central glutamatergic synapse inhibits presynaptic Ca(2+) currents (ICa) in a GluN2C/2D subunit-dependent manner, thereby decreasing nerve-evoked excitatory postsynaptic currents...
July 2017: Open Biology
https://www.readbyqxmd.com/read/28746305/stimulation-of-functional-neuronal-regeneration-from-m%C3%A3-ller-glia-in-adult-mice
#18
Nikolas L Jorstad, Matthew S Wilken, William N Grimes, Stefanie G Wohl, Leah S VandenBosch, Takeshi Yoshimatsu, Rachel O Wong, Fred Rieke, Thomas A Reh
Many retinal diseases lead to the loss of retinal neurons and cause visual impairment. The adult mammalian retina has little capacity for regeneration. By contrast, teleost fish functionally regenerate their retina following injury, and Müller glia (MG) are the source of regenerated neurons. The proneural transcription factor Ascl1 is upregulated in MG after retinal damage in zebrafish and is necessary for regeneration. Although Ascl1 is not expressed in mammalian MG after injury, forced expression of Ascl1 in mouse MG induces a neurogenic state in vitro and in vivo after NMDA (N-methyl-d-aspartate) damage in young mice...
July 26, 2017: Nature
https://www.readbyqxmd.com/read/28742157/angiotensin-ii-system-in-the-nucleus-tractus-solitarii-contributes-to-autonomic-dysreflexia-in-rats-with-spinal-cord-injury
#19
Kai Wang, Shaoxia Duan, Xueping Wen, Weizhong Wang, Shangping Fang, Dunyi Qi, Xiang Huan, Liwei Wang, Zhenzhou He
BACKGROUND: Autonomic dysreflexia (AD) is a potentially life-threating complication after spinal cord injury (SCI), characterized by episodic hypertension induced by colon or bladder distension. The objective of this study was to determine the role of impaired baroreflex regulation by the nucleus tractus solitarii(NTS) in the occurrence of AD in a rat model. METHODS: T4 spinal cord transection animal model was used in this study, which included 40 Male rats Colorectal distension (CD) was performed to assess AD and compare the changes of BP, HR, and BRS, six weeks after operation...
2017: PloS One
https://www.readbyqxmd.com/read/28741405/optimized-tpa-a-non-neurotoxic-fibrinolytic-agent-for-the-drainage-of-intracerebral-hemorrhages
#20
Romain Goulay, Mikaël Naveau, Thomas Gaberel, Denis Vivien, Jérôme Parcq
Intracerebral hemorrhage (ICH) is the most severe form of stroke. Catheter-delivered thrombolysis with recombinant tissue-type plasminogen activator (rtPA) for the drainage of ICH is currently under evaluation in a phase III clinical trial (MISTIE III). However, in a pig model of ICH, in situ fibrinolysis with rtPA was reported to increase peri-lesional edema by promoting N-methyl-D-aspartate (NMDA)-dependent excitotoxicity. In the present study, we engineered a non-neurotoxic tPA variant, OptPA, and investigated its safety and efficacy for in situ fibrinolysis in a rat model of ICH...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
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